The opioids are widely used clinically and abusively during pregnancy. It is well established that these drugs cause difficult management problems in the fetus and neonate. More subtle defects of the central nervous system which might be caused by exposure of the fetus to opioids are predictable but have never been subjected to systematic morphological analysis coupled with behavioral evaluation in the fetus. The nervous system develops morphologically in a clearly definable, orderly sequence which can be readily observed. Utilizing this, the more subtle effects on the nervous system of exposure of the fetus to opioids may be identified at the cellular and subcellular level to determine sites and times of action of these substances. The time of onset of analgesia and dependence will be determined by observing the effects of opioids and withdrawal on spontaneous and reflex activity "in utero." This will be correlated with the state of neural development. The substantia gelatinosa has been shown to have opiate receptors in adults and is the first nucleus in the pain pathway. Using binding studies and autoradiography it will be established that opiate receptors are located in the substantia gelatinosa of the fetal spinal cord and the time determined at which the receptors are first present. This information will be correlated with the state of cellular and subcellular development. One segment of the substantia gelatinosa of animals chronically exposed to morphine will be examined for the following: size of the nucleus; neuron size and number; length, size, and spine density of processes; neuron/glia ratios; and total cell number. Next, an ultrastructural profile of the substantia gelatinosa in one segment of morphine-dependent fetuses will be obtained and compared with normal animals. These experiments will provide two types of information - the state of the nervous system when the opioids become effective and the morphological changes caused by chronic exposure to opioids during development. This study provides a model for assessing the morphological liability of drugs on the developing nervous system.